The objectives of the project are to investigate the mechanisms involved in the control of cell proliferation in the mammalian small intestine. Appropriate experiments with rats are in progress. The compensatory response to resection of 70% of the combined ileum and jejunum is the baseline against which much of our future data will be compared. The increased proliferation rate persists many weeks after the surgical procedure; experiments are in progress to see if it lasts as long as 360 days. The influences of a second resection on cell proliferation rate and the changes in cyclic nucleotide levels will be investigated further. It has been found that a prior radiation exposure of the intestine prevents a full compensatory response to resection. This work will be extended to include X-ray exposures down to 10 R and the time interval between irradiation and resection will be varied. Our previous search for chalone-like substances in the intestinal mucosa or circulating blood of normal or resected rats will be continued.